While iPSC-CMs are valuable for arrhythmia modeling, their clinical translation requires overcoming significant arrhythmogenic risks through advanced maturation and gene editing techniques.
Background and Objectives: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have revolutionized cardiac research by providing patient-specific models for studying arrhythmias. However, their clinical application is hindered by arrhythmogenic risks associated with grafted iPSC-CMs. This review aims to delineate the current limitations in iPSC-CM-based arrhythmia modeling and explore emerging therapeutic strategies to mitigate these risks. Materials and Methods: A comprehensive literature review was conducted, focusing on studies published in the last two decades that address the electrophysiological characteristics of iPSC-CMs, their arrhythmogenic potential, and therapeutic interventions. Sources include peer-reviewed journals, clinical trial reports, and recent advancements in stem cell technology. Results: Findings indicate that while iPSC-CMs offer a promising platform for arrhythmia modeling, challenges such as cellular heterogeneity, immaturity, and proarrhythmic potential persist. Advancements in maturation protocols, co-culture systems, and gene editing techniques have shown promise in enhancing the safety profile of iPSC-CMs. Conclusions: Addressing the arrhythmogenic risks associated with iPSC-CMs requires a multifaceted approach, including improved differentiation protocols, maturation strategies, and therapeutic interventions. Continued research is essential to translate these models into safe and effective clinical applications.
Shahannaz et al. (Tue,) studied this question.